A population-based case-control study of non-Hodgkin's lymphoma (NHL) is proposed to include 900 newly diagnosed patients and 1800 controls in the San Francisco region. A rapid case-finding system will be used to identify cases newly diagnosed in all hospitals in the six-county San Francisco Bay Area during the period February 1988 through September 1992. Controls will be identified by random digit-dial, and will be frequency matched to cases by age, sex, and telephone number (area code and prefix). Structured personal interviews will be conducted by trained interviewers in study subjects' homes, or at a place they choose. Interview topics include: medical and occupational factors, prescriptive and other drug use, vaccinations, common allergies, other disturbances of the immune system, viral infections, travel to foreign countries, and among males, history of homosexual experiences. A sample of 200 NHL patients with AIDS-related diseases and a sample of 300 NHL patients without these diseases will be tested for antibodies to Human Immunodeficiency Virus (HIV) and Human T-lymphotropic Virus-I (HTLV-I). Serum will be saved to be tested later in the event a new virus is found to be associated with NHL. These data will be used to evaluate temporal trends in prevalence of positive antibodies to HIV in non-AIDS cases and to HTLV-I in both AIDS and Non-AIDS-related patients. T-cell subset analyses also will be performed on these patients. The lab results will be used with the questionnaire data to assess risk factors for NHL by histologic type and specific groupings of histologic types. Strengths of the project include: 1) the large number of NHL patients in the San Francisco Bay Area that provides adequate sample size to examine associations separately by sex and many subtypes; 2) the ability to observe viral seropositivity over the 5 years of the study and to relate trends in seropositivity to trends in NHL incidence; 3) the expertise and laboratory facilities available for the laboratory tests; 4) the large male homosexual population of San Francisco County, which will permit exploration of hypotheses relating risk for NHL to AIDS and HTLV-I; 5) rapid case-finding mechanism to minimize loss of study subjects, particularly those with high-grade NHL; 6) the population-based SEER tumor registry that provides complete case ascertainment for 5 of the 6 countries in this Bay Area study.